Th1-like cytokine production profile and individual specific alterations in TCRBV-gene usage of T cells from newly diagnosed type 1 diabetes patients after stimulation with beta-cell antigens.
In order to study cytokine production profile (IFN-gamma, IL-4 and TNF-alpha) and TCRBV-gene usage of peripheral autoreactive T cells from IDDM patients, we have generated antigen-specific T cell lines with either tetanus toxoid, insulinoma membranes or a single beta-cell protein, recombinant ICA69, which has been shown to be a target of both autoantibodies and T cells in IDDM. By semi-quantitative polymerase chain reaction (PCR) analysis, we have determined the composition of the T cell receptor repertoire of these T cell lines and compared this with the general peripheral repertoire. T cell responses against beta-cell antigens and tetanus toxoid (TT) were shown to be associated with IFN-gamma and TNF-alpha production, suggestive of a Th1-like phenotype of the T-cell lines. The production of IFN-gamma was significantly higher in T-cell lines generated with ISG compared to those generated with TT. The cytokine production profiles of the T-cell lines generated with ICA69 did not provide an obvious explanation for the inverse relation between cellular and humoral responses to this protein observed earlier. Upon stimulation with beta-cell antigens, outgrowth of T cells using a restricted set of TCRBV elements was observed in newly diagnosed IDDM patients. However, this skewing in TCRBV-gene expression was patient-specific rather than antigen-associated, since the T-cell repertoire that is used for the recognition of these antigens was, overall, heterogeneous.
Kallan
A A
AA
Department of Immunohaematology & Blood Bank, University Hospital, Leiden, The Netherlands.
Duinkerken
G
G
de Jong
R
R
van den Elsen
P
P
Hutton
J C
JC
Martin
S
S
Roep
B O
BO
de Vries
R R
RR
D000293:Adolescent; D000941:Antigens / Q000276:immunology / Q000494:pharmacology*; D001324:Autoantigens / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D019674:Genes, T-Cell Receptor beta; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007206:Individuality; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D013744:Tetanus Toxin / Q000494:pharmacology; D018417:Th1 Cells / Q000378:metabolism*
D000941:Antigens; D001324:Autoantigens; D016207:Cytokines; C087054:ICA1 protein, human; D007135:Immunoglobulin Variable Region; D007328:Insulin; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013744:Tetanus Toxin; D003208:Concanavalin A